The role of inducible 70-kDa heat shock protein in cell cycle control, differentiation, and apoptotic cell death of the human myeloid leukemic HL-60 cells

Cell Immunol. 1998 Jul 10;187(1):1-12. doi: 10.1006/cimm.1998.1309.


Several studies have suggested a role for heat shock proteins (hsps) during development and differentiation. However, relatively little is known about the role of hsp70 in controlling human hematopoietic cell differentiation and death. Here, we show that constitutive expression of human inducible 70-kDa heat shock protein (hsp70) promotes differentiation of HL-60 cells and prevents apoptosis that occurred after terminal differentiation or directly by apoptotic agents. After treatment with phorbol 12-myristate 13-acetate (PMA), hsp70-overexpressing cells (HL-60/hsp70) underwent rapid growth arrest and plastic adherence and expressed more CD14 than parental HL-60 or empty vector-transformed cells (HL-60/puro). HL-60/hsp70 cells also rapidly differentiated into granulocytes by addition of all-trans-retinoic acid, as assessed by phenotypic changes after staining with Wright-Giemsa. After differentiation into monocyte/macrophage-like cells or granulocytes, hsp70-overexpressing cells showed little evidence for apoptosis and had a prolonged survival, indicating that the survival-enhancing properties of hsp70 counteract programmed cell death that accompanies terminal differentiation. HL-60/hsp70 cells also showed more resistance than parental cells against apoptotic agents such as sodium nitroprusside, a NO-generating agent, or Taxol, a microtubule stabilizing agent. Further, heat shock of parental HL-60 cells at 42 degrees C for 3 h increased hsp70 levels, promoted plastic adherence (< 6 h) of the cells in respond to PMA, and protected cells from SNP or Taxol. Taken together, these studies demonstrate that hsp70 plays a crucial role in the differentiation of myeloid cells, participating in cell cycle controls and phenotypic changes, with protecting effects on apoptosis induced by different pathways.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Base Sequence
  • Cell Cycle / drug effects
  • Cell Cycle / physiology*
  • Cell Differentiation / drug effects
  • Cell Differentiation / physiology*
  • DNA Damage
  • DNA Fragmentation
  • DNA, Recombinant / genetics
  • Gene Expression
  • Granulocytes / cytology
  • Granulocytes / metabolism
  • HL-60 Cells
  • HSP70 Heat-Shock Proteins / biosynthesis
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / physiology*
  • Hematopoiesis / physiology
  • Humans
  • Macrophages / cytology
  • Macrophages / metabolism
  • Nitric Oxide / pharmacology
  • Nitroprusside / pharmacology
  • Paclitaxel / pharmacology
  • Tetradecanoylphorbol Acetate / pharmacology


  • DNA, Recombinant
  • HSP70 Heat-Shock Proteins
  • Nitroprusside
  • Nitric Oxide
  • Tetradecanoylphorbol Acetate
  • Paclitaxel